Receptor Positive Operable Breast Cancer Research Articles

The balance of clinician and patient input into treatment decision-making in older women with operable breast cancer.

Primary endocrine therapy (PET) is an alternative to surgery for oestrogen receptor positive operable breast cancer in some older women. However the decision to offer PET involves complex trade-offs and is influenced by both patient choice and healthcare professional (HCP) preference. This study aimed to compare the views of patients and HCPs about this decision and explore decision-making (DM) preferences and whether these are taken into account during consultations. This multicentre, UK, mixed methods study had three components: (a) questionnaires to older women undergoing counseling about breast cancer treatment options which assessed their DM preferences and realities; (b) qualitative interviews with older women with operable breast cancer offered a choice of either surgery or PET and (c) qualitative interviews with HCPs (both of which focused on DM preferences in this setting). Thirty-three patients and 34 HCPs were interviewed. A range of opinions about patient involvement in DM were identified. Patients indicated varying preferences for DM involvement which were variably taken into account by HCPs. These qualitative findings were broadly supported by the questionnaire results. Most patients (536/729; 73.5%) achieved their preferred DM style; however, the remainder felt that their DM preferences had not been taken into consideration. These results suggest that whilst many older women achieve their desired level of DM engagement, some do not, raising the possibility that they may be making choices which are not concordant with their treatment preferences.

Follow up after sample size re-estimation in a breast cancer trial for time to recurrence

In an international trial of premenopausal women with hormone receptor positive operable breast cancer that compares how the timing of surgical oophorectomy and mastectomy affects time to recurrence, we re-evaluated the required sample size near the end of the planned accrual period. We had anticipated that failure probabilities used at the design stage were too high resulting in a loss of power for the hazard ratio of interest. Extending follow up to obtain the number of events expected during the initial planning was not a viable option due to evidence in several previous trials of converging hazard functions. We proceeded to develop a method to re-estimate sample size in this time to event trial based on the blinded trial. Blinded re-estimation was our preference since we did not want to risk the perception that the sample size was manipulated because a smaller effect, than was anticipated, was found. Using data from a previous trial in a similar patient population receiving the same therapy (but who were not randomized to surgery timing) and the current blinded trial data, we re-estimated the required sample size. The distribution of bootstrap re-estimates of sample size indicated no increase in sample size was needed for the proposed HR. Follow-up for this trial is now complete. We will examine the final failure rates and hazard functions to see how well our re-estimation procedure performed. We will be able to explore if the hazard functions converged dramatically and what this impact would have been without this consideration.

Efficacy and Tolerability of Toremifene and Tamoxifen Therapy in Premenopausal Patients with Operable Breast Cancer: A Retrospective Analysis

Given the use of tamoxifen as standard treatment for hormone receptor-positive breast cancer, the use of toremifene as an adjuvant endocrine therapy has not been widely examined. The present retrospective study compared the efficacy and safety of toremifene and tamoxifen in the treatment of operable hormone receptor-positive breast cancer in premenopausal women. Premenopausal patients with hormone receptor- positive operable breast cancer were eligible. Enrolled patients (n = 1847) received either 60 mg toremifene (n = 396) or 20 mg tamoxifen (n = 1451) daily for a minimum of 5 years after surgery. Disease-free survival (dfs) was the primary endpoint. Overall survival (os) and time to distant recurrence were secondary endpoints. Treatment with toremifene and tamoxifen resulted in no between-group differences in dfs (p = 0.659) or os (p = 0.364). Mean dfs was 10.3 years for both groups. Mean os was 11.2 years for the toremifene group and 11.1 years for tamoxifen group. The 5-year dfs rate was 87.0% in the toremifene group and 85.0% in the tamoxifen group. The 5-year survival rate was 94.3% in the toremifene group and 93.5% in the tamoxifen group. Adverse events rates were similar in the two groups, with the exception of irregular menses, which occurred at a higher rate in the tamoxifen group than in the toremifene group (10.0% vs. 6.3%, p = 0.025). In this retrospective study, the efficacy and safety profiles of toremifene and tamoxifen for the treatment of operable hormone receptor-positive breast cancer in premenopausal women were similar.

Estrogen receptor positive operable breast cancer: Does menopausal status impact on HER2 and progesterone receptor status?

Purpose The objective of the present study was to determine whether progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status differs by menopausal status in estrogen receptor (ER)-positive breast cancers. Patients and methods We retrospectively analyzed the clinicopathological data of 588 with operable ER + breast cancers patients. ER, HER2 and PgR expression in the tumor specimens were examined by immunohistochemistry. The relationship between different variables was assessed by Pearson’s χ 2 and Fisher’s exact probability tests in univariate analyses. Logistic regression was used for multivariate analyses of relationship between HER2 expression and selected clinicopathological characteristics. Maximum likelihood estimates of the odds ratio (OR) were obtained and 95% confidence intervals (CI) were calculated. Results In the postmenopausal women with ER + tumors, HER2 was independently inversely associated with PgR expression ( P = 0.017; OR 3.02; 95% CI 1.22–7.49). An ER +/PgR − tumor was 3.02 times more likely to express HER2 than an ER +/PgR + tumor in the postmenopausal women. However, an ER + tumor in the premenopausal patients failed to show an independent relationship between HER2 and PgR. Conclusion Menopausal status played a very important role in determining HER2 and PgR status in ER + breast cancer patients. HER2 was independently inversely associated with PgR only in the postmenopausal women with ER + breast cancers but not in the premenopausal ones.

Effects on survival of menstrual cycle phase of adjuvant surgical oophorectomy in premenopausal women with breast cancer

Adjuvant surgical oophorectomy is an effective and remarkably cost effective treatment for premenopausal women with hormone receptor positive operable breast cancer. Previously published secondary analyses indicated a survival benefit for patients whose surgery was performed in the luteal phase of the menstrual cycle as opposed to the follicular. This study utilizes additional follow-up and more fully examines this hypothesis and the general implications of long-term follow-up on trial design. Beginning in 1993 we recruited women to a multicenter randomized clinical trial of adjuvant surgical oophorectomy and tamoxifen for 5 years. We recorded the reported day 1 of the patients' last menstrual cycle on the day of their adjuvant surgery. We conducted secondary analyses of the association of history-estimated luteal or follicular phase oophorectomy surgery with disease-free and overall survival. In multivariable Cox analyses, disease-free survival (DFS) exhibited a positive trend and overall survival (OS) showed a significant improvement in patients whose surgery was estimated to have occurred in the luteal phase of the menstrual cycle compared to the follicular (HR for DFS: 0.66, 95% CI: 0.37-1.16; HR for OS: 0.49, 95% CI: 0.27-0.88). From the hazard function plots, it appears that the luteal phase surgery effect on DFS diminishes after 6 years of follow-up. In conclusion, adjuvant surgical oophorectomy during the luteal phase of the menstrual cycle resulted in a reduced hazard of recurrence as compared to oophorectomy in the follicular phase during the first 5.5 years of follow-up. The practical and biological implications of these findings deserve rigorous evaluation in clinical trials.

Abstract S2-1: Obesity at Diagnosis Is Associated with Inferior Outcomes in Hormone Receptor Positive Breast Cancer

Abstract Background: Obesity has been associated with worse outcomes in operable breast cancer. We evaluated the effect of obesity on outcomes in several adjuvant trials coordinated by the ECOG which included doxorubicin/cyclophosphamide plus other agents, including E1199 (NEJM 2008; 358: 1663), E5188 (JCO 2005; 23: 5973) and E3189 (JCO 10998; 16: 2382). Methods: The relationship between body mass index (BMI in kg/m2) and disease free survival (DFS) and overall survival (OS) was evaluated in multivariate models adjusted for covariates including age, tumor size, nodal status, race (black vs. other), surgery type, prior RT, menopausal status, treatment arm, and treatment adherence. Results are expressed as hazard ratios (HR) from Cox's proportional hazards models (HR > 1 indicates a worse outcome). All p-values are two sided. Results: The study characteristics and results are shown in the table below. We first evaluated results for the E1199 trial (for the 75% of those with BMI data available) and found a non-significant trend toward inferior DFS (HR 1.10, 95% CI 0.96, 1.26, p=0.18) and OS (HR 1.13, 95% CI 0.96, 1.33, p=0.15) for obese subjects compared with others. When evaluated by breast cancer subtype, however, obese subjects with ER and/or PR-positive/HER2-negative disease had significantly inferior DFS (HR 1.24, p=0.026) and OS (HR 1.42, p=0.003), an effect that was not seen for HER2-positive and triple negative disease. In a model including obesity, ER and/or PR-pos/HER2-neg disease, and their interaction, the interaction term was significant for OS (p=0.017) but not DFS (p=0.21). There was no evidence for differing chemotherapy delivery or endocrine therapy adherence, or differences in toxicity for obese subjects in the E1199 trial. We then evaluated the relationship between obesity and outcomes in two prior ECOG studies which included only premenopausal women with ER positive, node positive breast cancer (E5188) and women of any age with ER/PR negative, node positive disease (E3189), and confirmed a relationship between obesity and poor outcomes only in women with hormone receptor positive disease. HR-hazard ratio; ER/PR-estrogen/progesterone receptor Conclusions: Obesity was associated with significantly inferior DFS and OS in hormone receptor positive operable breast cancer treated with adjuvant chemotherapy. These findings suggest that hyperinsulinemia or other factors associated with obesity may predispose to recurrence specifically in hormone receptor positive disease, and requires further evaluation in prospective studies in order to identify modifiable factors contributing to this effect. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S2-1.

Prognostic Utility of the 21-Gene Assay in Hormone Receptor–Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features

Prognostic Utility of the 21-Gene Assay in Hormone Receptor–Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features

Prognostic Utility of the 21-Gene Assay in Hormone Receptor–Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features

Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. A sample of 465 patients with hormone receptor (HR) -positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.

Cardiovascular Reserve and Risk Profile of Postmenopausal Women After Chemoendocrine Therapy for Hormone Receptor–Positive Operable Breast Cancer

Purpose. To examine cardiovascular function and risk profile of postmenopausal women treated with chemoendocrine therapy (CET) for hormone receptor-positive operable breast cancer. Methods. Forty-seven breast cancer patients and 11 age-matched healthy controls were studied. Participants performed a cardiopulmonary exercise test with expired gas analysis and impedance cardiography to assess peak aerobic power (VO(2peak)) and cardiovascular function (stroke volume, cardiac output, cardiac power output, and cardiac reserve). Traditional (i.e., body mass index, lipid profile, and fasting insulin and glucose) and novel (i.e., C-reactive protein, brain natriuretic peptide) cardiovascular risk biochemical factors were also assessed. Results. Breast cancer patients had significantly lower peak exercise stroke volume (68 +/- 9 versus 76 +/- 11 ml/beat), cardiac output (10.4 +/- 1.5 versus 11.7 +/- 2.4 l/minute), cardiac power output (3.0 +/- 0.5 versus 3.5 +/- 0.9 Watts), cardiac power output reserve (1.7 +/- 0.6 versus 2.4 +/- 0.8 Watts), and VO(2peak) (1.3 +/- 0.3 versus 1.6 +/- 0.2 l x min(-1)) than control subjects (p-values < .05). Patients with the greatest impairment in VO(2peak) had the worse cardiovascular risk profile. Exploratory analyses revealed several differences in study outcomes between the 26 patients receiving hormonal therapy with tamoxifen (TAM) and the 21 patients receiving aromatase inhibitor (AI) therapy. Conclusion. Breast cancer patients treated with adjuvant CET have a significantly and markedly lower cardiorespiratory fitness and cardiac functional reserve compared with age- and sex-matched controls. AI therapy may be associated with a more unfavorable cardiovascular risk profile than TAM. Prospective studies are required to further investigate the clinical value of these findings.